cGI PDEs are important in the regulation of myocardial contractility, vascular tonus, platelet aggregation and antilipolytic action of insulin. Four cGI PDEs have been recently cloned from human adipose tissue (HcGIP1), human heart (HcGIP2) and rat adipose tissue (RcGIP1 and P2). At the present time little is known concerning the types of cGI PDEs in tumor cells. In three human hepatoma cell lines (HepG2, Hep3B and HUH7) PDE activity is inhibited by the selective cGI PDE inhibitor OPC 3689. Whereas most of the cGI PDE in HepG2 and Hep3B is particulate, cGI PDE activity in HUH7 is found in both cytosolic and particulate fractions. From RT-PCR cloning of HepG2 cGI PDE cDNA using degenerate primers from either side of the additional region in the conserved catalytic domain of cGI PDEs an about 300 bp fragment was isolated with nucleotide sequence identical to HcGIP1. Poly A mRNA isolated from hepatomas hybridizes with HcGIP1 and HcGIP2 cDNAs. The mechanism(s) involved in the regulation of expression of cGI PDEs in the different hepatoma cell lines is unknown.